This is a proposal for continued NIH/NIGMS support for our COBRE in Stem & Progenitor Cell Biology and Regenerative Medicine as we transition from successful Phase-ll status to a critical stage of Phase-Ill development. Prime goals are: i) Continue to advance thematic, biomedically relevant discoveries in stem and progenitor cell biology; ii) Sustain and extend strong internal and external advisory committees and supporting mechanisms to expertly mentor investigators, fellows, students and core staff; iii) Implement a Pilot Project Program to springboard highly promising discoveries towards national funding and impacting publications; iv) Work with our highly supportive Medical Center and Research Institute to recruit additional strong COBRE Center investigators; v) Continue to sharpen the expertise, efficiency, utility and selfsustaining nature of our Center's Research Core Facilities. During Phase-ll, we have further advanced impacting discoveries in our discipline, published studies in excellent journals, mentored and advanced Center investigations, recruited strong new investigators, and demonstrated clear success in securing independent national funding. Gains in infrastructure and Institutional support also are significant. These include the construction of a new research wing, the ongoing recruitment of additional scientists, the advancement of existing core facilities, and the development of a highly needed Physiology Core. In Phase-Ill, the PI will be assisted administratively by a co-lnvestigator (L. Oxburgh, PhD, DVM COBRE member since 2005) and Program Coordinator (E. Jachimowicz). Our administrative core will implement a Pilot Project Program for outstanding seed investigations, and to advance new translational research opportunities; a core workshop and summer symposium in Stem & Progenitor Cell Biology; an invited seminar series; and the recruitment of a magnet clinician scientist. Core facilities also will be enhanced. The Molecular Phenotyping Core focuses on quantitative molecular analysis of gene expression and cellular microscopy. The Histopathology Core provides expert histological support plus new collaborations involving human pathology studies, and mouse genetic mutants. Our Progenitor Cell Analysis Core provides flow cytometric analyses, cell sorting, clonal cell analyses and stem/progenitor cell culture services. Our new Physiology Core will provide state-of-the-art metabolic phenotyping, skeletal imaging and cell energetic analyses. Specific plans towards Core and Center self-sufficiency post- Phase-Ill also are defined.